spacer gif spacer gif spacer gif spacer gif spacer gif
 QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online April 23, 2007
doi: 10.1242/10.1242/jcs.003129


Journal of Cell Science 120, 1646-1653 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nawshad, A.
Right arrow Articles by Hay, E. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nawshad, A.
Right arrow Articles by Hay, E. D.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

TGFbeta3 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex

Ali Nawshad1,*,{ddagger}, Damian Medici2,*, Chang-Chih Liu1 and Elizabeth D. Hay2

1 Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583, USA
2 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA

{ddagger} Author for correspondence (e-mail: anawshad{at}unmc.edu)

Accepted 5 March 2007

Dissociation of medial-edge epithelium (MEE) during palate development is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGFbeta3 upon adherence of opposing palatal shelves, because loss of E-cadherin causes the MEE seam to break into small epithelial islands. To investigate the molecular mechanisms that cause this E-cadherin loss, we isolated and cultured murine embryonic primary MEE cells from adhered or non-adhered palates. Here, we provide the first evidence that lymphoid enhancer factor 1 (LEF1), when functionally activated by phosphorylated Smad2 (Smad2-P) and Smad4 (rather than beta-catenin), binds with the promoter of the E-cadherin gene to repress its transcription in response to TGFbeta3 signaling. Furthermore, we found that TGFbeta3 signaling stimulates epithelial-mesenchymal transformation (EMT) and cell migration in these cells. LEF1 and Smad4 were found to be necessary for up-regulation of the mesenchymal markers vimentin and fibronectin, independently of beta-catenin. We proved that TGFbeta3 signaling induces EMT in MEE cells by forming activated transcription complexes of Smad2-P, Smad4 and LEF1 that directly inhibit E-cadherin gene expression.

Key words: E-cadherin, LEF1, Smad, TGF-beta, Epithelial-m


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
A. Chatterjee, L. Wang, D. L. Armstrong, and S. Rossie
Activated Rac1 GTPase Translocates Protein Phosphatase 5 to the Cell Membrane and Stimulates Phosphatase Activity in Vitro
J. Biol. Chem., February 5, 2010; 285(6): 3872 - 3882.
[Abstract] [Full Text] [PDF]


Home page
JDRHome page
L. Meng, Z. Bian, R. Torensma, and J.W. Von den Hoff
Biological Mechanisms in Palatogenesis and Cleft Palate
Journal of Dental Research, January 1, 2009; 88(1): 22 - 33.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
D. Medici, E. D. Hay, and B. R. Olsen
Snail and Slug Promote Epithelial-Mesenchymal Transition through {beta}-Catenin-T-Cell Factor-4-dependent Expression of Transforming Growth Factor-{beta}3
Mol. Biol. Cell, November 1, 2008; 19(11): 4875 - 4887.
[Abstract] [Full Text] [PDF]




© The Company of Biologists Ltd 2007